Microfluidic flow control devices

ABSTRACT

Various microfluidic flow control devices are provided. In one embodiment, a regulating device includes overlapping channel segments separated by a deformable membrane in fluid communication with one another. In another embodiment, a normally open microfluidic valve provides latching valve operation with at least one adhesive surface. A stencil-based microfluidic valve may be operated by deforming a membrane against a seating surface to prevent flow through an aperture. Configurable microfluidic devices permit flow control among an interconnected microfluidic channel network. Magnetic elements may be integrated into flexible membranes to provide magnetically actuated microfluidic flow control device.

STATEMENT OF RELATED APPLICATION(S)

[0001] This application claims benefit of U.S. application Ser. No.60/246,138, filed on Nov. 6, 2000.

FIELD OF THE INVENTION

[0002] The present invention relates to microfluidic devices and thecontrol of fluid flow within those devices.

BACKGROUND OF THE INVENTION

[0003] There has been a growing interest in the manufacture and use ofmicrofluidic systems for acquiring chemical and biological information.In particular, when conducted in microfluidic volumes, complicatedbiochemical reactions may be carried out using very small volumes ofliquid. Among other benefits, microfluidic systems increase the responsetime of reactions, minimize sample volume, and lower reagentconsumption. When volatile or hazardous materials are used or generated,performing reactions in microfluidic volumes also enhances safety andreduces disposal quantities.

[0004] Traditionally, microfluidic systems have been constructed in aplanar fashion using techniques borrowed from the silicon fabricationindustry. Representative systems are described, for example, in someearly work by Manz et al. (Trends in Anal. Chem. (1990) 10(5): 144-149;Advances in Chromatography (1993) 33: 1-66). These publications describethe construction of microfluidic devices using photolithography todefine channels on silicon or glass substrates and etching techniques toremove material from the substrate to form the channels. A cover plateis bonded to the top of the device to provide closure.

[0005] More recently, a number of methods have been developed that allowmicrofluidic devices to be constructed from plastic, silicone or otherpolymeric materials. In one such method, a negative mold is firstconstructed, and then plastic or silicone is poured into or over themold. The mold can be constructed using a silicon wafer (see, e.g.,Duffy et al., Analytical Chemistry (1998) 70: 4974-4984; McCormick et.al., Analytical Chemistry (1997) 69: 2626-2630), or by building atraditional injection molding cavity for plastic devices. Some moldingfacilities have developed techniques to construct extremely small molds.Components constructed using a LIGA technique have been developed at theKarolsruhe Nuclear Research center in Germany (see, e.g., Schomburg etal., Journal of Micromechanical Microengineering (1994) 4: 186-191), andcommercialized by MicroParts (Dortmund, Germany). Jenoptik (Jena,Germany) also uses LIGA and a hot-embossing technique. Imprintingmethods in polymethylmethacrylate (PMMA) have also been demonstrated(see, e.g., Martynova et aL, Analytical Chemistry (1997) 69: 4783-4789).However, these techniques do not lend themselves to rapid prototypingand manufacturing flexibility. Moreover, the tool-up costs for suchtechniques are quite high and can be cost-prohibitive.

[0006] Typically, flow control within microfluidic devices has beenprovided through the application of electric currents to causeelectrokinetic flow. Systems for providing such utility are complicatedand require electrical contacts to be present. Additionally, suchsystems only function with charged fluids, or fluids containingelectrolytes. Finally, these systems require voltages that aresufficiently high as to cause electrolysis of water, thus formingbubbles that complicate the collection of samples without destroyingthem. Therefore, there exists a need for a microfluidic device capableof controlling flow of a wide variety of fluids without using electricalcurrents.

[0007] Some of the basic challenges involved in operating microfluidicsystems result from attempts to interface between conventional“macro-scale” devices and microfluidic components. Due to the very smallcross-sectional area of microfluidic channels, flow through thesechannels can be quite sensitive to pressure variations. Assuming that anexternal pressure source is used to motivate fluid flow in amicrofluidic system, a number of applications would benefit if the flowrate of a flowing fluid could be controlled in spite of variations ininput pressure. For example, such control can be especially valuable inperforming reactions such as chemical or biological synthesis. To reduceoverall costs and provide versatility, it would be desirable to achievecontrolled fluid flow within a microfluidic device using variouslow-precision pressure sources, such as, for example, a conventionalmanually-operated syringe or an inexpensive, low-precision syringe pump.Also in the interest of reducing costs, it would be desirable to providecontrolled fluid flow in a microfluidic device with a minimum of movingparts or control components. Thus, there exists a need for a simple yetrobust microfluidic regulating device capable of receiving fluid from alow-precision source and providing a controlled fluid flow rate in spiteof fluctuations in input pressure.

[0008] A microfluidic device with limited (i.e., on-off) flow controlcapability is provided in U.S. Pat. No. 5,932,799 to Moles (“the Moles′799 patent”). There, polyimide layers enhanced with tin (between400-10,000 ppm) are surface micromachined (e.g., etched) to formrecessed channel structures, stacked together, and then thermally bondedwithout the use of adhesives. A thin, flexible valve member actuated byselective application of positively or negatively pressurized fluidselectively enables or disables communication between an inlet and anoutlet channel. The valve structure disclosed in the Moles ′799 patentsuffers from numerous drawbacks that limit its utility, however. First,the valve is limited to simple on-off operation requiring a constantactuation signal, and is incapable of regulating a constant flow.Second, the valve is normally closed in its unactuated state. It isoften desirable in microfluidic systems to provide normally open valvestructures subject to closure upon actuation. Third, the Moles ′799patent teaches the fabrication of channels using time-consuming surfacemicromachining techniques, specifically photolithography coupled withetching techniques. Such time-consuming methods not only require highsetup costs but also limit the ability to generate, modify, and optimizenew designs. Fourth, the Moles ′799 patent teaches only fabrication ofdevices using tin-enhanced polyimide materials, which limits theirutility in several desirable applications. For example, polyimides aresusceptible to hydrolysis when subjected to alkaline solvents, which areadvantageously used in applications such as chemical synthesis. Theinclusion of tin in the device layers may present other fluidcompatibility problems. Finally, polyimides are generally opaque to manyuseful light spectra, which impedes their use with common detectiontechnologies, and further limits experimental use and quality controlverification.

[0009] Another microfluidic valve structure having limited utility isdisclosed in WIPO International Publication Number WO 99/60397 to Holl,et al. There, a microfluidic channel is bounded from above by a thick,deformable elastic seal having a depressed region that protrudes throughan opening above the channel. An actuated external valve pin pressesagainst the elastic seal, which is extruded through the opening into thechannel in an attempt to close the channel. This valve, however, suffersfrom defects that limit its utility. To begin with, it is difficult tofabricate an elastic seal having a depressed region to precisely fitthrough the opening above the channel without leakage. Additionally, thevalve provides limited sealing utility because it is difficult to ensurethat the extruded seal completely fills the adjacent channel,particularly in the lower corners of the channel. Further, the contactregion between the external valve pin and the elastic seal is subject tofrictional wear, thus limiting the precision and operating life of thevalve.

[0010] Using conventional technologies, it is generally difficult toquickly generate and modify designs for robust microfluidic devices. Toinclude flow control capability in such a device only elevates thatdifficulty. It would be desirable to provide a “generic” microfluidicplatform that could be quickly and easily tuned with various componentsand/or materials to provide different flow control utilities dependingon the particular application, taking into account varying designcriteria such as the operating fluid, the flow rates, and the pressuresinvolved. If available, such a platform would promote rapid prototypingand device optimization at a substantially reduced cost compared toconventional technologies.

[0011] Additionally, it would be desirable to enable flow through amicrofluidic channel network to be externally controlled without theattendant drawbacks of electrokinetic or electrophoretic flow. Inparticular, it would be desirable to provide a channel network havingmultiple inlets and multiple outlets, and be able to selectivelyestablish fluid flow paths through the network between one or morespecific inlets and one or more specific outlets. If available, such adevice could be used as a versatile fluid “switch.” It would beparticularly desirable if this fluid switching utility could beexternally programmed so as to execute repetitive and/or sequentialfunctions with minimal user interaction. Preferably, a fluid switchingdevice or system would be simple and robust with a minimum number ofparts subject to wear.

[0012] Finally, conventional “on-off” microfluidic valve structures suchas the valve disclosed in the Moles ′799 reference require constantapplication of a control signal, thus consuming external actuationresources for as long as a valve state is to be maintained. To reducethe consumption of external actuation resources and provide othercapabilities including fluid logic functions, it would be desirable toprovide robust microfluidic valves with “latching” capability, in otherwords, the ability to maintain position in an actuated state withoutcontinuous application of an actuation signal. These and other needs anddesirable aspects are addressed herein.

SUMMARY OF THE INVENTION

[0013] In a first separate aspect of the invention, a microfluidicregulating device includes a first and a second channel segment definedin different layers of a microfluidic device and in fluid communicationwith one another. A membrane separates the channel segments at aregulatory region. In the presence of a pressure differential betweenthe two channel segments, the membrane is deformed toward and into thechannel segment having a lower internal pressure, thus reducing fluidflow capability through the first or the second channel segment.

[0014] In another separate aspect of the invention, a normally openmicrofluidic flow control device includes a first and a secondmicrofluidic channel each defined in different stencil layers. Fluidcommunication may be established between the first and the secondchannel through an aperture defined in a valve seating surface. Adeformable membrane centrally disposed above or below the aperture iscapable of being deformed to seal against the valve seating surface,thus preventing fluid flow through the aperture.

[0015] In another separate aspect of the invention, a microfluidic flowcontrol device includes a microfluidic channel bounded by a lowersurface, by lateral channel walls, and by a deformable membrane capableof being deformed by actuation means into the channel and against thelower surface. At least one of the lower surface and the first membranehas an adhesive surface capable of maintaining contact between the lowersurface and the first membrane after disactivation of the actuationmeans.

[0016] In another separate aspect of the invention, a microfluidic flowcontrol device includes a first control layer and a second control layereach defining multiple channel segments. A channel layer, which defininga microfluidic channel network in fluid communication with multiplefluid inlet ports and fluid outlet ports, is disposed between the firstand the second control layer. A flexible membrane separates the firstcontrol layer and the channel layer, and a flexible membrane separatesthe second control layer and the channel layer. Fluid flow paths betweenone or more specific inlet ports and one or more specific outlet portsmay be selectively established by manipulating pressure withinindividual control channels, thus causing deformation of the firstand/or the second membrane into the channel network at one or more valveregions.

[0017] In another separate aspect of the invention, a microfluidic flowcontrol device includes a first and a second microfluidic channelcapable of being in fluid communication, and a deformable membranecapable of affecting fluid flow between the two channels. A magneticelement is associated with the deformable membrane. Application of amagnetic field deforms the deformable membrane.

[0018] In another separate aspect of the invention, a configurablemicrofluidic device includes a network of interconnected fluid channelsand multiple first and second control channels. The first and secondcontrol channels are separated from the network of interconnectedmicrofluidic channels by at least one deformable membrane at one or moreregulatory regions.

[0019] In another aspect of the invention, any of the foregoing separateaspects may be combined for additional advantage.

[0020] These and other aspects and advantages of the present inventionwill become apparent from the following detailed description of thepreferred embodiments taken in conjunction with the figures.

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] FIGS. 1A-1C are cross-sectional views of at least a portion ofmicrofluidic device constructed from 5 layers of material, the devicehaving a deformable membrane separating equally-sized upper channelregion and a lower channel region. FIG. 1A illustrates the membrane in aneutral position. FIG. 1B illustrates the membrane being deflectedtoward and into the lower channel region. FIG. 1C illustrates themembrane being deflected toward and into the upper channel region.

[0022] FIGS. 2A-2B are cross-sectional views of at least a portion of a5-layer microfluidic device having a larger upper channel region and asmaller lower channel region. FIG. 2A illustrates the membrane beingdeformed toward and into the smaller, lower channel region. FIG. 2Billustrates the membrane being deformed toward and into the larger,upper channel region.

[0023] FIGS. 3A-3E are cross-sectional views of at least a portion of amicrofluidic device having three separate channel regions (an upper, acentral, and a lower channel region) divided by two deformable membranes(an upper and a lower membrane). FIG. 3A illustrates both membranes inneutral positions. FIG. 3B illustrates the upper deformable membranebeing deflected toward and into the central channel region. FIG. 3Cillustrates both the upper and the lower deformable membrane beingdeflected toward and into the central channel region. FIG. 3Dillustrates the lower deformable membrane being deflected toward andinto the central channel region. FIG. 3E illustrates both the upper andlower deformable membrane being deflected away from the central channelregion, namely, the upper deformable membrane being deflected toward andinto the upper channel region, and the lower deformable membrane beingdeflected toward and into the lower channel region.

[0024]FIG. 4A is an exploded perspective view of a five-layermicrofluidic device having a pressure-activated regulating valve thatcontrols fluid flow within the device. FIG. 4B is a top view of theassembled device of FIG. 4A.

[0025]FIG. 5A is a top view of a portion of one layer of at least aportion of a microfluidic device, the layer having a network ofinterconnected channels. FIG. 5B is a top view of portions of twoadditional, superimposed layers of the same device shown in FIG. 5A, thetwo additional layers defining control channels for directing fluid flowwithin the channel network illustrated in FIG. 5A. FIG. 5C is a top viewof a membrane that may be used in the device illustrated in FIGS. 5A-5B,the membrane composed of different membrane materials in four regions.FIG. 5D is a top view of a membrane similar to the membrane illustratedin FIG. 5C, but composed of different membrane materials in sixteenregions. FIG. 5E is a top view of the superimposed layer portions ofFIGS. 5A-5B and two membranes assembled into a microfluidic device, withschematic illustration of the device being operated to define onepossible fluid flow path. FIG. 5F is a schematic illustration of amicrofluidic flow control system including the microfluidic device ofFIG. 5E coupled to at least one pressure source and a controller, amongother components.

[0026]FIG. 6A is an exploded perspective view of a five-layermicrofluidic device capable of delivering a relatively constant flowrate of fluid over a large range of pressures. FIG. 6B is a top view ofthe assembled device of FIG. 6A. FIG. 6C is a cross-sectional view of aportion of the microfluidic device of FIGS. 6A-6B along section lines“A-A” shown in FIG. 6B, with the regulatory region in the open position.FIG. 6D provides the same cross-sectional view as FIG. 6C, but with theregulatory region in the closed position.

[0027]FIG. 6E is a chart showing the flow rates achieved at theunregulated and regulated outlets of the device shown in FIGS. 6A-6Dover a range of input pressures, with each outlet tested separatelywhile the other outlet was sealed. FIG. 6F is a chart showing the flowrates at both the unregulated and regulated outlets of the device shownin FIGS. 6A-6D over a range of input pressures, measured with bothoutlets open.

[0028]FIG. 7A is a cross-sectional view of a portion of a microfluidicdevice having three channel segments that meet at a regulatory regionand that are separated by a single deformable membrane. FIG. 7B providesthe same cross-sectional view as FIG. 7A, but with the membranedeflected toward and into the upper channel segment.

[0029]FIG. 8A is a cross-sectional view of a deformable membrane havinga magnetic element affixed to the membrane. FIG. 8B is a cross-sectionalview of a deformable membrane formed with two membrane layers laminatedaround a magnetic element. FIG. 8C is a cross-sectional view of adeformable membrane formed with a central magnetic element, two outermembrane layers and a central stencil layer.

[0030]FIG. 9A is a cross-sectional view of a magnetic field generatingelement microfluidic flow control device and at least a portion of amicrofluidic flow control device having a magnetic element laminatedwithin a membrane layer, the membrane being in a relaxed state. FIG. 9Bprovides the same cross-sectional view as FIG. 9A, but with the membranein a deformed state to prevent flow between two microfluidic channelswithin the flow control device.

[0031]FIG. 10 is a perspective view of a magnetic field generator arraydisposed above a microfluidic flow control device having multiple fluidinlets and outlets and multiple magnetic elements associated withflexible membranes to provide flow control utility.

[0032]FIG. 11 is a schematic illustration of a microfluidic flow controlsystem showing interconnections between a microfluidic flow controldevice, a magnetic field generator array, and a controller, among othercomponents.

[0033]FIG. 12A is a cross-sectional view of at least a portion of amicrofluidic device having a deformable membrane disposed above anaperture permitting fluid communication between two channels. FIG. 12Bprovides the same cross-sectional view as FIG. 12A, but with themembrane deformed to seal the aperture and prevent fluid communicationbetween the two channels.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

[0034] Definitions

[0035] The term “channel” as used herein is to be interpreted in a broadsense. Thus, it is not intended to be restricted to elongatedconfigurations where the transverse or longitudinal dimension greatlyexceeds the diameter or cross-sectional dimension. Rather, the terms aremeant to include cavities, tunnels, or chambers of any desired shape orconfiguration through which liquids may be directed. Such a fluid cavitymay, for example, comprise a flow-through cell where fluid is to becontinually passed or, alternatively, a chamber for holding a specified,discrete amount of fluid for a specified amount of time. “Channels” maybe filled or may contain internal structures comprising valves orequivalent components.

[0036] The term “channel segment” as used herein refers to a region of achannel.

[0037] A “change in channel segment shape and geometry” indicates anychange in the dimensions of a channel segment. For instance, the channelsegment can become smaller, larger, change shape, be completely closed,be partially closed, be permanently restricted, etc.

[0038] The term “microfluidic” as used herein is to be understood,without any restriction thereto, to refer to structures or devicesthrough which fluid(s) are capable of being passed or directed, whereinone or more of the dimensions is less than 500 microns.

[0039] The term “stencil” as used herein refers to a material layer thatis preferably substantially planar, through which one or more variouslyshaped and oriented portions has been cut or otherwise removed throughthe entire thickness of the layer, and that permits substantial fluidmovement within the layer (e.g., in the form of channels or chambers, asopposed to simple through-holes for transmitting fluid through one layerto another layer). The outlines of the cut or otherwise removed portionsform the lateral boundaries of microstructures that are formed uponsandwiching a stencil between substrates and/or other stencils.

[0040] Fabrication of Microfluidic Devices

[0041] Microfluidic devices providing flow control utility according tothe present invention may be fabricated in various ways using a widevariety of materials. In an especially preferred embodiment,microfluidic devices according to the present invention are constructedusing stencil layers to define channels and/or chambers. As described infurther detail in co-pending U.S. application Ser. No. 09/453,029 filedDec. 1, 1999, which is hereby incorporated by reference as if fully setforth herein, a stencil layer is preferably substantially planar and hasmicrostructure cut through the layer. For example, a computer-controlledplotter modified to accept a cutting blade may be used to cut variouspatterns through a material layer. Alternatively, a computer-controlledlaser cutter may be used. As further alternatives, conventionalstamping, cutting, and/or molding technologies may be employed to formstencil layers. The wide variety of materials that may be used tofabricate microfluidic devices using sandwiched stencil layers includepolymeric, metallic, and/or composite materials, to name a few. Notably,use of stencil-based fabrication methods enables a particular devicedesign to be rapidly “tuned” or optimized for particular operatingparameters, since different material types and thicknesses may bereadily used and/or substituted for individual layers within a device.The ability to prototype devices quickly with stencil fabricationmethods permits many different variants of a particular design to betested and evaluated concurrently.

[0042] When assembled in a microfluidic device, the top and bottomsurfaces of stencil layers may mate with one or more adjacent stencil orsubstrate layers to form a substantially enclosed device, typicallyhaving one or more inlet ports and one or more outlet ports. In oneembodiment, one or more layers of a device are comprised of single- ordouble-sided adhesive tape, although other methods of adhering stencillayers may be used. A portion of the tape (of the desired shape anddimensions) can be cut and removed to form channels, chambers, and/orapertures. A tape stencil can then be placed on a supporting substrate,between layers of tape, or between layers of other materials. In oneembodiment, stencil layers can be stacked on each other. In thisembodiment, the thickness or height of the channels can be varied byvarying the thickness of the stencil (e.g., the tape carrier and theadhesive material thereon) or by using multiple substantially identicalstencil layers stacked on top of one another. Various types of tape areuseful with this embodiment. Suitable tape carrier materials include butare not limited to polyesters, polycarbonates, polytetrafluoroethlyenes,polypropylenes, and polyimides. Such tapes may have various methods ofcuring, including curing by pressure, temperature, or chemical oroptical interaction. The thicknesses of these carrier materials andadhesives may be varied.

[0043] Alternatively, microfluidic devices according to the presentinvention are fabricated from materials such as glass, silicon, siliconnitride, quartz, or similar materials. Various conventional machining ormicromachining techniques such as those known in the semiconductorindustry may be used to fashion channels, vias, and/or chambers in thesematerials. For example, techniques including wet or dry etching andlaser ablation may be used. Using such techniques, channels, chambers,and/or apertures may be made into one or more surfaces of a material orpenetrate through a material.

[0044] Still further embodiments may be fabricated from variousmaterials using well-known techniques such as embossing, stamping,molding, and soft lithography.

[0045] In addition to the use of adhesives or single- or double-sidedtape discussed above, other techniques may be used to attach one or moreof the various layers of microfluidic devices useful with the presentinvention, as would be recognized by one of ordinary skill in attachingmaterials. For example, attachment techniques including thermal,chemical, or light-activated bonding; mechanical attachment (such asusing clamps or screws to apply pressure to the layers); or otherequivalent coupling methods may be used.

[0046] Microfluidic Membrane Valves

[0047] In various embodiments of the present invention, membranes areused in microfluidic devices to provide flow control utility. In oneembodiment, a microfluidic device includes a first microfluidic channelsegment and a second microfluidic channel segment that are separated bya deformable membrane at a regulatory region. The channels may bedefined in horizontal layers of a device, with the deformable membraneforming a separate horizontal layer separating the channel layers. Thechannels can overlap at any suitable angle. The channels may beorthogonal, thus limiting the area of the overlap region, or they may besubstantially parallel. The first and second channels also can be influid communication. Where the channels are in fluid communication, theuse of the terms first channel segment and second channel segment referto regions forming a channel disposed on different layers of the device.A change in relative pressure between the first and second channelsresults in deformation of the membrane separating the channels. Themembrane is deformed towards the channel segment with lower relativepressure. The membrane can partially block flow of the fluid through thechannel segment with lower relative pressure or can substantially blockflow of the fluid through the channel segment with lower relativepressure. The degree of deformation of the deformable membrane isrelated to the differential pressure between the first and secondchannels. Generally, the greater the differential pressure, then thegreater the observed deformation of the deformable membrane.

[0048] FIGS. 1A-1C illustrate at least a portion of a microfluidicdevice 90 having a deformable membrane 102 that is responsive to changesin pressure between two channel segments 105, 106. The channel segments105, 106 may be defined in stencil layers 101, 103 disposed betweenouter layers 100, 104. The deformable membrane 102 separates the firstchannel segment 105 defined in layer 101 from the second channel segment106 defined in layer 103. When the pressures in channels 105 and 106 aresubstantially the same, then the deformable membrane 102 adopts aneutral position, as shown in FIG. 1A. If the pressure in channelsegment 105 is increased, or the pressure in channel segment 106substantially decreased, then the deformable membrane 102 will deformtowards channel segment 106, as shown in FIG. 1B. When a sufficientdifferential pressure is attained, the deformable membrane 102(specifically the lower surface 107 of the membrane 102) may contact theupper surface 108 of the outer layer 104. When the pressure in channelsegment 106 is substantially increased or that in channel segment 105substantially decreased, the deformable membrane 102 may deform into thechannel segment 105, as shown in FIG. 1C. When a sufficient differentialpressure is attained, the deformable membrane 102 (specifically, theupper surface 109) will contact the lower surface 110 of substrate layer100.

[0049] As noted previously, the channel segment-containing portion ofthe device 90 can be constructed using any suitable materials, by anysuitable technique. In a particularly preferred embodiment, amicrofluidic device is constructed with sandwiched stencil layers. Thelayers of the device containing channel segments may also be constructedfrom etched silicon, molded polymers, or using other materials orfabrication methods known to one skilled in the art of makingmicrofluidic devices. For example, in the device 90 illustrated in FIGS.1A-1C, the channel segment 105 could be surface etched into a singleintegral substrate substituted for separate layers 100 and 101.Likewise, channel segment 106 could be etched into a single integralsubstrate substituted for separate layers 103 and 104.

[0050] Microfluidic devices described herein may be constructed usingstill further techniques. In certain embodiments, channels areconstructed in materials using etching, embossing, or moldingtechniques. Two or more different elements may be constructed. Then, themultiple elements may be assembled face-to-face with a deformablemembrane disposed between them. The channels in the two etched orembossed devices may overlap in certain areas of the completed devicewith the deformable intermediary layer between the channel segments.Additionally, one or more apertures may be defined in the intermediatelayer to serve as vias connecting the channels in the upper and lowerdevices. More complicated systems can be constructed.

[0051] Control of the properties of the microfluidic device can beachieved by varying the deformable membrane material. The material canbe elastically deformable or can be inelastically deformable. Suitablemembrane materials include papers, foils and polymers. In a preferredembodiment, the membrane is a polymer including, for example,polyesters, polycarbonates, polytetrafluoroethylenes, polypropylenes,polyimides (e.g., KAPTON®) and polyesters (e.g., MYLAR®), silanes (e.g.,PDMS) and polymethylmethacrylate (PMMA). A more rigid material willdeflect less readily due to a change in pressure, while a more malleablematerial will deflect more easily. A membrane material also can bechosen based on its ability to perform repeated deformation cycles.

[0052] The sensitivity of microfluidic device to changes in differentialpressure may also be controlled by varying the thickness of thedeformable membrane. Generally, a thinner membrane material will be moreeasily deformed and will respond more easily to changes in differentialpressure. A thicker membrane will generally be less easily deformed andwill be less sensitive to changes in relative pressure. The thickness orheight of the channel segment into which the deformable channel segmentmoves also will impact the fluid control performance of the system.

[0053] Another technique for adjusting the sensitivity of themicrofluidic system to changes in relative pressure is to change thearea of the regulatory region or deformable membrane. Adjacentmicrofluidic channels or chambers separated by a deformable membrane maybe fashioned in a wide variety of sizes, shapes, and geometries. Channelor chamber segments can overlap in a perpendicular format, at an angleor along a length of channel segment that is parallel. Channels within aregulator region may be formed with constant widths or variable widths.One example of a regulatory region is provided in FIGS. 6A-6B, in whichthe regulatory region 207 is circular.

[0054] The areas of adjacent channel segments opposite the membrane atthe regulatory region may also be different from one another. The largerthe deformable membrane, for example, the more easily it providesubstantially complete blockage of fluid flow in the adjacent channelsegment. FIGS. 2A-2B show at least a portion of a microfluidic device299 having, at the valve location, a relatively large channel segment305 and a smaller channel segment 306 separated by deformable membrane302. When the relative pressure in the larger channel segment 305 ishigher than that in the smaller channel segment 306, the membrane 302 inthe valve region deforms toward and into the smaller channel segment306, as shown in FIG. 2A. The small relative size of channel segment 306means that the deformable membrane 302 only reduces the available crosssection of channel segment 306 to about half its original size. However,when the relative pressure in channel segment 306 is higher than thepressure in channel segment 305, then the membrane 302 deforms towardand into the larger channel segment 305, as shown in FIG. 2B. Because ofthe relatively large area of the channel 305 bounded by the deformableportion of the membrane 302, the membrane 302 is able to move moreeasily into channel segment 305, thereby significantly changing thecross section of the channel segment 305. For example, a membrane havinga deformable portion 5 mm in diameter will deflect across a 3-mil (75microns) channel segment more readily than a 2 mm diameter deformablemembrane portion, because there is less of a percentage of deformationof the larger membrane.

[0055] In a preferred embodiment, a channel subject to fluidic controldefines an aperture opposite and substantially aligned with the centerof a deformable membrane. In such a configuration, a fluid flow path isprovided in a direction parallel to the direction of travel of thedeformable membrane. For example, FIG. 6C shows at least a portion of amicrofluidic device having a channel segment 207 in fluid communicationwith an aperture 210 aligned substantially centrally below thedeformable membrane 202. Deformation of the membrane 202 towards channelsegment 207 results in substantially complete blockage of fluid flowbetween channel segments 210 and 207. While similar devices can beconstructed with the aperture disposed in various positions relative tothe path of the deformable membrane, it is highly preferable to positionthe aperture near to the center of travel of the deformable a membraneto promote substantial blockage of the fluid flow path by the membrane.The size of the aperture will also affect the amount of pressurerequired to provide substantially leak-free sealing.

[0056] Using these techniques, a system can be constructed in whichdeformation of the material results in either partial blockage orsubstantially complete blockage of fluid flow through a channel segment.An elastic material may be used where reversible control of fluid flowis desired. Lowering the pressure in the higher relative pressurechannel segment allows the deformable membrane to resume its neutralstate, allowing unrestricted fluid flow. In certain applications, it isdesirable to provide substantially permanent or irreversible change to amicrofluidic channel segment. For example, it may be desirable for asystem to provide shut-off valving utility to protect downstreamcomponents from damage caused by high flow or pressure. Upon increase inpressure in one channel segment, an inelastic material will beplastically deformed towards the channel segment with lower pressure.The material will remain substantially in the deformed position. Suchresults may be obtained with semi-malleable materials including suitablemetal foils.

[0057] A deformable membrane also can be made of materials with surfaceproperties that alter its behavior. For example, a membrane can be tackyor have an adhesive coating. Such properties or coatings can be appliedto one or both sides of the deformable membrane. Depending on thestrength of the adhesive or degree of tackiness, the deformable membranecan operate as a variable switch. At low relative pressures, themembrane can act elastically. At high pressures, or for systems designedfor the deformable membrane to physically contact the opposing wall ofthe adjacent channel segment, the deformation can result in permanent orsemi-permanent closure of the adjacent channel segment. In anotherembodiment, the membrane used can be non-adhesive, but the surfaceagainst which it seals can be constructed with a tacky or adhesivesurface. For example, in FIG. 1B, the lower surface 107 of thedeformable membrane 101 can be coated with an adhesive, or can beconstructed from an adhesive tape, such that upon deformation sufficientto provided contact between the membrane 102 and the lower layer 104,the deformable membrane 102 can be affixed to the upper surface 108 ofthe lower layer 104. The degree of permanence of the closure depends onfactors including elasticity of the membrane and the strength of theadhesive material used. Similar results can be achieved by coating theupper surface 108 with adhesive or both surfaces 107 and 108 withadhesive, or by forming one or more of these surfaces from single- ordouble-sided self-adhesive tape materials. Referring to FIG. 1B, thebottom surface of the membrane 107 or the upper surface 108 of thebottom layer 104 may include permanent or semi-permanent adhesives. Whenthe membrane 102 is deformed, such as by an elevated pressure within theupper chamber 105, then the membrane 102 may be deformed to contact thelower layer 104 to permit the adhesive to bind the surfaces together andpermanently or semi-permanently obstruct the lower channel segment 106.

[0058] In certain embodiments, the membrane 102 may be deformed andadhered to the lower surface in a semi-permanent manner that may bereversed by further manipulation. For example, when pressure is appliedto 105, the membrane 102 is deformed so as to the contact the lowerlayer 104, where the membrane 102 and the upper surface 108 of the lowerlayer 104 are adhesively bound. Alternatively, the membrane 102 may beplastically deformed into the lower channel 106. When the pressure isre-equalized between the upper and lower chambers 105, 106, the membrane102 will remain affixed to the lower layer 104 until sufficient pressureis applied to channel segment 106 to overcome the adhesive bond orplastic deformation of the membrane 102. In many cases, the pressurerequired to reposition (i.e., re-deform) the membrane 102 may be greaterthan the pressure to originally deform it.

[0059] In another embodiment, a microfluidic valve may include twomicrofluidic channels separated by a seating surface defining anaperture for mating with a deformable membrane to provide flow controlutility. For example, FIGS. 12A-12B illustrate a microfluidic device 197fabricated from seven layers 200-204, 220, 221 and having a controlchannel 205 bounded in part by a deformable membrane 202. With thedeformable membrane in a relaxed, neutral state, fluid flow may beestablished between a first channel 207 and a second channel 222 definedin different layers 203, 220 of the device 197 and separated by aseating layer 204 defining an aperture 210. The deformable membrane 202is disposed substantially centrally above the aperture 210 to promotetight sealing of the aperture when the control channel 205 ispressurized to deform the membrane 202 to contact the seating layer 204,as shown in FIG. 12B. The valve seating layer 210 adjacent to theaperture 210 may be considered a valve seating surface. The device 197thus serves as a normally open valve that permits flow through theaperture when the deformable membrane is in an undeformed state.Selective pressurization of the control channel 205 permits closure ofthe valve. Either or both of the membrane 202 and the seating layer 204may be provided with an adhesive surface to provide latching valveutility.

[0060] In further embodiments, more complex fluid control structuresutilizing multiple membranes may be formed. For example, more than twochannels can meet at a valve region separated by one or more membranes.In certain embodiments, more than one pressure regulator may be stackedin a given vertical position of a microfluidic device. In oneembodiment, three channels overlap at a single valve region, with twodeformable membranes separating the various channels. FIGS. 3A-3E showfive cross-sectional views of such an overlap. FIG. 3A shows across-section of at least a portion of a microfluidic device 119 formedusing sandwiched stencils, the device having seven layers 120-126 andforming three channel segment/chamber regions 127-129. In thisembodiment, the central stencil layer 123 has a greater height than theother layers, and the layers 122 and 124 are flexible or deformablemembranes. Fluid flow through the central channel segment 128 isaffected by both the upper chamber region 127 and the lower chamberregion 129. FIG. 3B shows the central channel segment 128 beingpartially blocked following a pressure increase within the upper chamber127, causing deflection of the upper membrane 122 toward and into thecentral channel 128. FIG. 3C shows the channel segment 128 beingsubstantially (almost completely) blocked following pressure increasesin both the upper and lower chamber 127, 129, which cause both membranes122, 124 to deform toward and into the central channel 128. FIG. 3Dshows another operating state wherein the channel segment 128 ispartially blocked following a pressure increase in the lower chamberregion 129. In FIG. 3E, the central channel segment 128 is enlarged inresponse to a reduced pressure in both the upper and lower chambers 127,129.

[0061] In the operation of a device of the invention, a differentialpressure can be generated between a first and a second channel segmenteither by increasing the pressure in one channel segment, or through arelative decrease in pressure in one channel segment. The pressure of afluid (encompassing both liquids and gases) can be increased by a pumpsuch as, for example, a syringe or other mechanically operated pump.Reduced pressure can be achieved in the channel segment by applying avacuum to a channel segment, for example using a vacuum pump. Where achannel segment is pressurized to greater than atmospheric pressure anda pressure reduction is desired, then the pressure can be reduced byventing the channel segment to the atmosphere or to a lower-pressurereservoir. Pressure can also be controlled by changing the temperaturewithin one channel segment of the device. In such an embodiment, it ispreferred that the fluid within the channel segment undergoes a largevolume change with changing temperature. Preferably, in such anembodiment the fluid is a gas. The pressure can be increased by raisingthe temperature of the gas within the channel segment and can bedecreased by lowering the temperature within the channel segment. Thepressure within a channel segment also can be changed by processes suchas vaporization or electrolysis (a process in which an electric currentis used to break a liquid within a channel segment into gaseouscomponents). For example, water may be electrolyzed into hydrogen gasand oxygen gas.

[0062] Microfluidic membrane valves may be actuated with means otherthan pressure. For example, a membrane can be moved within a devicemanually or with a mechanical actuator. Mechanical actuators include,for example, a piston, a solenoid, and a lever. The flexible membranealso can be coupled to a material that alters shape in response to astimulus, for example, heat or an electric current. Titanium-Nickelcomposites are known that undergo large conformational changes inresponse to changes in temperature. Such a composite can be incorporatedinto the deformable membrane. When heated, as by passing an electriccurrent through the composite, the composite will change shape anddeflect the deformable membrane. The membrane also can be constructed ofa magnetic material, or provided with a magnetic coating. As will bediscussed further hereinafter, deformation of such a membrane can beachieved using an external magnet, including an electromagnet or anelectric field generator.

[0063] Microfluidic membrane valves may be combined into more complexdevices. The embodiments shown in FIGS. 3A-3E and others form the basicsof microfluidic logic elements. For example, the embodiment shown formsa microfluidic AND/OR element. Consider measuring the flow in thecentral channel 128 at a constant backpressure. In FIG. 3A, the flowthrough the channel 128 may be considered to be 1 unit, in FIG. 3B about{fraction (1/2)} of one unit, in FIG. 3C about 0 units, in FIG. 3D about½ of one unit, and in FIG. 3E about 2 units. It follows that: IF P127 =P128 AND P128 = P129 THEN Flow = 1 IF P127 = P128 AND P128 < P129 OR IFP129 = P128 AND P128 < P127 THEN Flow =< 1 IF P127 > P128 AND P129 >P128 THEN Flow =<< 1 IF P127 < P128 AND P129 < P128 THEN Flow => 1

[0064] In another preferred embodiment, the flow control elements shownin FIGS. 3A-3E can be combined in a network in order to make a twodimensional fluid control system. Referring to FIG. 5A, a network ofchannels 150 are defined in the center layer of a three dimensionaldevice. The channel network has multiple inlet ports 151 and outletports 152. Any given inlet port is in fluidic connection with all of theoutlet ports in the unaltered layer. When assembled in a flow controldevice 180, the channels 150 depicted in FIG. 5A will be disposedbetween control channels and flexible membranes, such as the channelsegment 128 shown in FIGS. 3A-3E.

[0065] Two control layers are also made within the device, one disposedabove and one disposed below the channel network 150. Referring to FIG.5B, the upper control layer of the three-dimensional device includesfour vertical control channels 160-163, and the lower control layer ofthe device has four horizontal control channels 156-159. These controlchannels 160-163 and 156-159 overlap in specific regions 155. Thecross-section of each of these overlap regions 155 are the same as thoseshown in FIGS. 3A-3E. Thus, control channels 160-163 are represented incross section by the channel segment 127 in FIGS. 3A-3E and the controlchannels 156-159 are represented in cross section by the channel segment129 of FIGS. 3A-3E.

[0066] Two flexible membranes, one disposed on either side of thechannel network 150, separate the channel network 150 from the upper andlower control layers. These membranes may be homogeneous membranelayers, or they may be heterogeneous layers to permit the valving orflow control characteristics at any particular region to be “tuned.”Examples of heterogeneous membrane layers are provided in FIGS. 5C-5D.In FIG. 5C, a first heterogeneous membrane layer 175 is composed of fourmembrane regions 175A-175D, any of which may be formed of differentmaterials to provide desired response characteristics for each quadrantof four nodes or intersections of control channels. In FIG. 5D, a secondheterogeneous membrane layer 176 is composed of sixteen membrane regions176A-176P to permit the response characteristics for each individualoverlap region 155 to be separately tuned if desired.

[0067] Referring to FIG. 5E, the various layers of the flow controldevice 180 may be assembled in the following order: a lower substrate, alower control channel layer, a lower flexible membrane layer, a centralchannel network layer, an upper flexible membrane layer, an uppercontrol channel layer, and finally an upper substrate or cover. In use,any given inlet port 151 can be connected to any given outlet port 152by simply controlling the pressures of the control channels 160-163 and156-159. This may be accomplished with a fluid control system 320 suchas illustrated in FIG. 5F. There, the pressure to individual controlchannels 156-159 and 160-163 is supplied by two pressure sources 302,304 and regulated by control valves 326A-326D and 328A-328D, which arepreferably three-way valves or the equivalent to permit excess air to bereleased if necessary. Each valve 326A-326D and 328A-D is controlled bya controller 313. The controller 313 is preferably electronic, and morepreferably microprocessor-based. The controller 313 may be programmed toexecute complex, sequential or repetitive fluid functions on the device180. One or more sensors 329 may be in sensory communication with themicrofluidic flow control device 180 and coupled to the controller 313to provide feedback and/or sensory data to be stored in or otherwiseused by the controller. An input device 331 and display 332 may becoupled to the controller 313 to aid with programming and processingsensory data, among other functions.

[0068] An example showing operation of the microfluidic device 180 isshown in FIG. 5E. In this example, a pressure of 20 psi (138 kPa) isapplied to control channel segment 157, negative 10 psi (69 kPa) isapplied to control channel segment 160, and positive 10 psi (69 kPa) isapplied to control channel segment 159. All of the other controlchannels are left at atmospheric pressure. All of the fluid channelsunder control channel segment 157 are blocked, because 10 psi (69 kPa)is sufficient to substantially block the channels. The valve regions ofinterest are 170, 171, and 172. At point 170, the upper control chamberhas 20 psi (69 kPa), and the bottom control chamber has −10 psi (69 kPa)for a net of +10 psi (69 kPa), which is sufficient to locally block thefluid channel in network 150. At point 171, the bottom has negative 10psi and the channel segment is opened more. At point 172, the +10 psi(69 kPa) applied to the top control channel equals the −10 psi (69 kPa)applied to the bottom control channel, and the central channel segmentremains open. For the rest of the channels along the control channel159, all are closed because they experience 10 psi (69 kPa). Thus, thefluid supplied to the central channel layer 150 through the input ports151 can only take the pathway shown by the arrow. Alternatively, anyoutlet port 152 can be reached by varying the pressure combinations tothe control channels 156-159 and 160-163.

[0069] In a further embodiment, a flow control device can have more thanone channel segment on a given layer at a regulatory region. As shown inFIGS. 7A-7B, a microfluidic device 699 includes two channel segments 706and 707 defined in layer 703 and separated by a deformable membrane 702from a channel segment 705 defined in an upper layer 701. The deformablemembrane 701 is not adhered a seating region 703A defined in the layer703. When the pressure in the channel segment 705 is high relative toboth channels 706 and 707, then fluid communication between the channels706 and 707 within the regulatory region is prevented by the membrane702 pressed into contact with the seating region 703A, such as shown inFIG. 7A. If the relative pressures in both channels 706 and 707 arehigher than that in the channel 705, such as shown in FIG. 7B, then themembrane 702 will deform toward and into the channel segment 705, thusallowing fluidic passage between the channels 706 and 707. Factorsaffecting whether an increased pressure in channel segments 706 or 707is sufficient to open a flow path between the channels indude the sizeof the seating region, the thickness and composition of the flexiblemembrane 702, and the size of the regulatory region (which affects thesize of the membrane subject to deformation).

[0070] Flow Control Devices with Feedback

[0071] In further embodiments, pressure-sensitive regions may beintegrated into a microfluidic device to provide internal feedback, suchthat a change in pressure or flow rate within one region of a channelsegment will affect another region.

[0072] In a preferred embodiment, a feedback loop is used to create apressure regulation device. A microfluidic device is constructed where afirst channel segment located in one layer of a three-dimensional deviceis in fluid communication with a second channel segment in another layerof the device. For example, the two channels in distinct layers may beconnected through a via or through-hole between layers. In an upperlayer, one channel segment is positioned so that it passes back over theother channel segment in a lower layer. This upper section can pass overthe lower region one or more times and can pass over the channel segmentin parallel along its axis or cross the channel segment at an angle. Adeformable membrane separates the two channel segments at a regulatoryregion. A pressure increase in the upstream part of the channel segmentwill cause the first channel segment to expand, thus compressing theoverlapping downstream part of the channel segment. This will deform themembrane towards the second channel segment, altering the shape orgeometry of the second channel segment. The flow through the secondsegment also can decrease, and will vary depending on the design of theregulatory region and with the pressure applied. The membrane canprovide a partial blockage or a substantially complete blockage to fluidflow through one channel segment. A subsequent decrease in the pressurewithin the channel segment will result in said channel segment attainingits previously unrestricted or “relaxed” neutral state.

[0073] A pressure-activated valve can regulate flow between two channelsegments in a single microfluidic channel because of the pressure-dropthat occurs “downstream” in microfluidic channels. The pressure within amicrofluidic channel decreases with distance from the inlet port. At lowinput pressures, there is a minimal pressure drop in a long channelsegment. As the input pressure increases, it becomes more difficult forthe internal pressures to equalize, and the pressure differential fromone end of a channel segment to the other is much larger. The higher theoperating pressure of the microfluidic device, the greater the pressuredifferential generated over the length of a channel. Thus, by designingdifferent microfluidic systems having valves separated by differentlengths of channel between one side of the pressure membrane and theother, different shut-off pressures can be designed or “programmed” intothe device. For example, in FIGS. 6A-6B (which is discussed in furtherdetail below), a relatively long channel segment connects the one sideof the shut-off valve membrane and the other; a long channel segmentlength is preferably provided to create the pressure differential.

[0074] A microfluidic device with a built in pressure regulation systemis shown in FIGS. 4A-4B. Referring to FIG. 4A, a microfluidic device 130was constructed using a sandwiched stencil fabrication method from fivelayers 131-135. The first layer 131 defines one inlet port 136 and twooutlet ports 137, 138. The second layer 132 defines two vias 140 and achannel segment 139 having a nominal width of 40 mils (1000 microns).The third layer 133 defines a central via 141 and two lateral vias 142.The fourth layer 134 defines a channel 143 also having a nominal widthof 40 mils (1000 microns). All of the vias are 70 mils in diameter. Thelayers 131-134 stencil layers are all constructed from 3 mil (75microns) thickness single-sided tape comprising a polypropylene carrierwith a water-based adhesive. The bottom stencil 100 is a 0.25 inch (6.3mm) thick block of acrylic.

[0075] In use, fluid is injected at inlet port 136 at a lowbackpressure. The fluid passes through channel segment 139 until itreaches junction point 144. The fluid then splits evenly down the twoparts of channel segment 143 until it reaches the outlet ports 137 and138. As fluid continues to flow, the fluid splits evenly at the junctionpoint 144 and is divided evenly. When increased pressure was applied atthe entry port 136, the pressure within the channel segment increased,as did the flow rate. In the region 145 where channels 139 and 143overlap, the pressure in the upper channel segment 139 pushes on thepolymeric membrane 133 that separates the two channels. The polymermaterial 133 is locally deformed and partially blocks the lower channelsegment 143, thus partially restricting the flow in that channelsegment.

[0076] In a preferred embodiment directed to this example, the size ofthe exit channels are adjusted such that the flow out of the device 130remains constant no matter what backpressure is applied. This device 130may be used in various applications, including but not limited toconstant delivery of materials such as in drug delivery applications. Ina preferred embodiment, inlet port 136 is connected to a pressurizedcontainer of fluid (not shown) that contains a drug of interest. Theoutlet ports 137, 138 are connected to a delivery mechanism to a body.When the pressurized container is full, the backpressure is high and theoutlet 137 is closed and 138 is open. Although the pressure remainshigh, the resistance in the channels is even higher since there is onlyone outlet. As the pressurized body loses fluid, the pressure decreaseswhich permits the exit port 137 to slowly open. As the pressure drops,the resistance in the channels decreases since two channels are nowopen. A more complicated structure with many feedback loops can beconstructed so that approximately constant flow can be maintained over alarge range of input pressures.

[0077] In a further embodiment, a microfluidic device was constructed toregulate flow rate over a large range of input pressures. Referring toFIGS. 6A-6B, a microfluidic flow regulation device 199 was constructedusing a stencil fabrication method from five layers 200-204. Startingfrom the bottom, the first layer 204 defined one inlet port 209 and twooutlet ports 210, 211. The second layer 203 defined a via 214 and achannel 206 terminating at a chamber 207. The third layer 202 definedtwo vias 208, 208A. The fourth layer 201 defined a channel 205 andconnected chamber 215. The fifth layer 200 served as a cover for thefourth layer 201. The assembled device is shown in FIG. 6B. The overlapregion 212 is shown in cross section in FIGS. 6C-6D with the valve inopen and closed positions, respectively. In use, fluid is injected intothe inlet port 209. The fluid travels through the vias 214, 208, throughchannel segment 205, down through the via 208A and the channel 206 andis split towards the two exit ports 210 and 211. When the inlet pressureis relatively low, the flexible membrane 202 is not substantiallydeformed (see FIG. 6C) and the fluid passes evenly out of the two exitports 210, 211. As the pressure at the inlet is increased, the pressurein the channel 205 and chamber 215 increases, thus deforming themembrane 202 (see FIG. 6D) and partially blocking the outlet port 210.

[0078] Two sets of experiments were performed with this device 199. Inthe first experiment, the pressure versus flow characteristic of the twoexit ports 210 and 211 were measured independently. One of the exitports was completely blocked, and the pressure at the inlet 209 versusflow at the outlet was measures. Referring to FIG. 6E, for exit port 211(unregulated), the flow rate increases as the pressure increases, aswould be expected. However, for the (regulated) exit port 210, as thepressure increases above 3 psi (21 mPa), the membrane 202 is deformed,resulting in a constricted channel segment. The device 199 acts as aflow regulator. As the pressure increases further, the flow remainsconstant since flow is proportional to pressure and channel segmentdimension. As the pressure increases, the channel segment dimensiondecreases, resulting in substantially constant flow rates.

[0079] The same experiment was repeated when both channels were measuredsimultaneously. The results of this experiment are provided in FIG. 6F.Again, the flow is regulated, but in this case, the flow is regulated toan even lower flow rate.

[0080] A structure substantially similar to that illustrated in FIGS.6C-6D is provided in FIGS. 12A-12B, with the primary difference beingthe addition of outlet channels 222 defined by stencil layer 220 and asubstrate 221 to continue flow within the device 197.

[0081] Magnetically actuated flow control devices

[0082] In another embodiment, a flow control device such as a valve ismagnetically actuated. Generally, magnetic actuation requires a fieldgenerator and a magnetic (i.e,, paramagnetic or ferromagnetic) element.The magnetic element moves in response to application of a magneticfield, with the direction of motion of the magnetic element depending onthe direction of the applied magnetic field. Opening or closing force ofa magnetically actuated valve may be adjusted by varying the magnitudeof the applied magnetic field, or selecting a magnetic element withappropriate response characteristics (e.g., magnetization). For example,if strong magnetization is desirable, then magnetic elements formed fromrare earth magnetic materials may be used.

[0083] Preferably, at least one magnetic element is integrated into amicrofluidic flow control device and used in conjunction with adeformable membrane. In a preferred embodiment, a deformable membraneincludes one or more discrete magnetic elements. A discrete magneticelement may be attached to a deformable membrane using various meansincluding adhesives and mechanical retention. For example, FIG. 8Aillustrates a magnetic element 400 affixed to a deformable membrane 401using an adhesive. In a more preferred embodiment shown in FIG. 8B, adiscrete magnetic element 402 is sandwiched between multiple deformablemembrane layers 403, 404. Contact between the layers 403, 404 and themagnetic element 402 may be maintained with an adhesive, such as if oneof the layers 403 is formed of a self-adhesive tape material. Furtherpreferably, as shown in FIG. 8C, a central membrane layer 407 may be astencil layer defining an aperture into which a magnetic element 405 maybe inserted. Multiple membrane layers 406-408 may be laminated togetherusing conventional bonding methods such as, for example, adhesive orthermal bonding. In a preferred embodiment, at least one membrane layercontaining the discrete magnetic element comprises a self-adhesive tapematerial. Adhesiveless films of deformable materials such as latex,polypropylene, polyethylene, and polytetrafluoroethylene are readilyavailable in thicknesses of approximately 0.5 mil (13 microns) or less.If supplied as self-adhesive tape, such materials are readily availablewith a total (carrier plus adhesive) thickness between approximately 1.5and 2.0 mils (38 to 50 microns). An embodiment such as shown in FIG. 8Bmay thus be provided with a combined membrane thickness of approximately2.0 to 2.5 mils (50 to 63 microns). In an embodiment such as shown inFIG. 8C, the central layer 407 may be a stencil layer formed of contactadhesive, so as to form a laminated membrane of approximately the sametotal thickness as before (approximately 2.0 to 2.5 mils, or 50 to 63microns).

[0084] A discrete magnetic element to be integrated with a membranelayer may be provided in any size or shape sufficient to promote thedesired flow control characteristics. If the flow control deviceutilizes a valve seat of a particular geometry, then the desired shapeand size of the magnetic element is preferably selected to interfacewith the valve seat geometry. Particular shapes of magnetic elementsthat may be used include cylindrical, spherical, or annular shapes. Avalve seat may include an aperture that may be selectively sealed tocontrol fluid flow. Preferably, the membrane may be deformed by magneticforce to seal the aperture, thus preventing fluid flow. Alternatively,an annular magnetic element may be disposed adjacent to an aperturedefined in a membrane, so that under certain conditions fluid ispermitted to flow through both the membrane aperture and the annularmagnetic element. This fluid flow path may be selectively blocked orre-established through application of a magnetic field that deforms themembrane against a valve seating surface.

[0085] As an alternative to using one or more discrete magneticelements, a flexible membrane comprising a diffuse magnetic layer may beprovided. If a diffuse magnetic layer is used, then it is preferablycoupled to a deformable membrane selected for desirable materialproperties such as chemical compatibility or sealing characteristics.

[0086] The magnetic field generator preferably comprises a coil ofcurrent-carrying wire, preferably insulated wire. Current mayselectively applied to the coil, such as by using an external currentsource, to generate a magnetic field. The strength of the magnetic fieldmay be adjusted by varying the magnitude of the current and the numberof turns of wire. The direction of the resulting magnetic field isparallel to the central axis of the coil. In a more preferredembodiment, a field-concentrating element, such as a ferromagnetic core,is provided along the central axis of the coil. A magnetic fieldgenerator 425 having a field-concentrating element 427 and a coil ofinsulated wire 426 is shown in FIGS. 9A-9B. The field-concentratingelement 427 is preferably substantially cylindrical in shape, and if ahighly focused field is desired then the cylinder should be of a smalldiameter. The current-carrying wire 426 may be directly wrapped aroundthe field-concentrating element 427.

[0087] As further shown in FIGS. 9A-9B, a magnetically actuated membranevalve is operated by selectively applying current to the coil 426. Todeform the membrane 411 (formed from laminated layers 411A-411C andmagnetic element 417) in one direction, current in one direction isapplied to the coil 426. To reverse the travel of the membrane 411,current is applied in the opposite direction. FIG. 9A shows the membrane411 in a relaxed position, with the field generator 425 substantiallycentered above the magnetic element 417, which in turn is substantiallycentered over an aperture 420 permitting fluid communication between afirst channel segment 418 and a second channel segment 419 within amicrofluidic flow control device 410. The flow control device 410 isformed from a three-layer composite membrane 411 and four other devicelayers 413-416. FIG. 9B shows the membrane 411 in a deformed positionand contacting the seating layer 414 adjacent to the aperture 420 toprevent fluid flow between the first channel segment 418 and the secondchannel segment 419.

[0088] In a preferred embodiment, multiple magnetically actuated flowcontrol valves may be integrated into a single microfluidic device.Referring to FIG. 10, a microfluidic flow control device 430 includes atleast one flexible membrane and multiple discrete magnetic elements 431.Preferably, the device 430 may be used to manipulate fluid betweenmultiple fluidic inlet ports 432 and multiple outlet ports 433. Amagnetic field generator array 435 having multiple coils and fieldconcentrating elements 436 may be positioned in relatively closeproximity to the microfluidic flow control device 430 to manipulatefluid within the device 430. However, the field generator array 435preferably does not contact the microfluidic device 430. Preferably, onecoil and field focusing element 436 is provided and paired with eachmagnetic element 431. One advantage of using field focusing elements insuch a device is to minimize unwanted interference between unpairedcoils and magnetic elements. High density arrays of field generators maythus be used to provide precise control over fluid flowing in a smallarea. Complex operation of a fluidic system can thus be provided withoutrequiring any external to ever physically contact the device 430. Forexample, utility similar to that described in connection with FIGS.5A-5F may be provided.

[0089] Various elements of a magnetically actuated microfluidic flowcontrol system 450 and their interconnections are illustratedschematically in FIG. 11. Preferably, a controller 442 is provided toselectively apply currents to the various field generator coils 436,such as may be contained in a field generator array 435. The controller442 is preferably electronic, and more preferably ismicroprocessor-based, and receives power from a power source 444. In apreferred embodiment, the controller 442 is programmable to permitexecution of complex, repetitive and/or sequential functions withminimal user interaction. Preferably, one or more sensors 440 areincluded in sensory communication with the microfluidic device 430 toprovide feedback and/or useful data to the controller 442. Suitablesensors may include, for example, pressure sensors, flow sensors,optical sensors, and displacement sensors. If the provided sensors arecapable of inferring fluid flow, then the system may be used to provideflow regulation utility. More specifically, feedback from a flow sensormay be provided to the controller 442, which in turn may provide ananalog signal to one or more field generators to regulate flow.Alternatively, pressure regulation utility may be provided in a similarfashion. An input device 446 and display 448 are preferably coupled tothe controller 442 to aid in programming and/or analyzing data generatedby the system 450.

[0090] The particular devices and construction methods illustrated anddescribed herein are provided by way of example only, and are notintended to limit the scope of the invention. The scope of the inventionshould be restricted only in accordance with the appended claims andtheir equivalents.

What is claimed is:
 1. A microfluidic regulating device comprising: afirst channel segment defined in a first layer of the device andcontaining a fluid flow; a second channel segment defined in a secondlayer of the device, the second channel segment being in fluidcommunication with the first channel segment; and a membrane separatinghe first channel segment and the second channel segment at a regulatoryregion; wherein the presence of a pressure differential between thefirst channel segment and the second channel segment causes the membraneto deform toward and into the channel segment having a lower internalpressure, thus reducing fluid flow capability through the first channelsegment or the second channel segment.
 2. The microfluidic regulatingdevice of claim 1 wherein at least one of the first device layer and thesecond device layer comprises a sandwiched stencil layer.
 3. Themicrofluidic regulating device of claim 1 wherein at least one of thefirst device layer, the second device layer, and the membrane has anadhesive surface.
 4. The microfluidic regulating device of claim 1wherein at least one of the first device layer, the second device layer,and the membrane comprises a self-adhesive tape material.
 5. Themicrofluidic regulating device of claim 3 wherein, when a pressuredifferential of sufficient magnitude is attained, the deformablemembrane contacts and is adhered to either the first device layer or thesecond device layer.
 6. The microfluidic regulating device of claim 1wherein the membrane is elastically deformable.
 7. The microfluidicregulating device of claim 1 wherein the membrane is a polymericmaterial selected from the group consisting of polyesters,polycarbonates, polytetrafluoroethylenes, polypropylenes, polyimides,polysilanes, polymethylmethacrylates, and polyesters.
 8. A microfluidicflow control device comprising: a first microfluidic channel defined ina first stencil layer a valve seating surface defining an aperture; asecond microfluidic channel defined in a second stencil layer, thesecond microfluidic channel capable of fluid communication with thefirst microfluidic channel through the aperture; and a deformablemembrane substantially centrally disposed above or below the apertureand capable of being deformed to seal against the valve seating surface,thus preventing fluid flow through the aperture; wherein fluid ispermitted to flow through the aperture when the deformable membrane isin an undeformed state.
 9. The microfluidic flow control device of claim8 wherein at least one of the deformable membrane and the valve seatingsurface has a self-adhesive surface.
 10. The microfluidic flow controldevice of claim 8, further comprising a control channel bounded by thedeformable membrane, wherein pressure within the control channel may bemanipulated to deform the membrane.
 11. A microfluidic flow controldevice comprising: a microfluidic channel bounded from below by a lowersurface and laterally by channel walls; a first deformable membranedefining an upper surface of the microfluidic channel, the firstmembrane capable of being deformed into the microfluidic channel; andactuation means capable upon activation of deforming the first membraneinto the microfluidic channel and into contact with the lower surface;wherein at least one of the lower surface and the first membrane has anadhesive surface capable of maintaining contact between the lowersurface and the first membrane after disactivation of the actuationmeans.
 12. The microfluidic flow control device of claim 11 furthercomprising a stencil layer defining the channel walls that serve as thelateral boundaries of the microfluidic channel, wherein the lowersurface is distinct from the stencil layer.
 13. The microfluidic flowcontrol device of claim 11 wherein the lower surface comprises a seconddeformable membrane capable of being deformed into the microfluidicchannel.
 14. The microfluidic flow control device of claim 11 whereinthe actuation means is selected from the group consisting of: manual,mechanical, pneumatic, hydraulic, electric, magnetic, and thermoelectricactuation.
 15. The microfluidic flow control device of claim 11 whereinat least one of the lower surface and the first membrane comprises aself-adhesive tape material.
 16. A microfluidic flow control devicecomprising: a first control layer defining a plurality of first controllayer channel segments; a second control layer defining a plurality ofsecond control layer channel segments; a channel layer disposed betweenthe first control layer and the second control layer, the channel layerdefining a microfluidic channel network in fluid communication with aplurality of inlet ports and a plurality of outlet ports; a firstmembrane separating the first control layer and the channel layer at aplurality of valve regions; and a second membrane separating the secondcontrol layer and the channel layer at a plurality of valve regions;wherein fluid flow paths between one or more specific inlet ports andone or more specific outlet ports may be selectively established bymanipulating the pressure within individual control layer channelsegments to cause deformation of the first membrane and/or the secondmembrane toward and into the channel network at one or more valveregions.
 17. The microfluidic flow control device of claim 16 wherein atleast one of the first control layer, the second control layer, and thechannel layer comprises a stencil layer.
 18. The microfluidic flowcontrol device of claim 16 wherein at least one of the first controllayer, the second control layer, the channel layer, the first membrane,and the second membrane has an adhesive surface.
 19. The microfluidicflow control device of claim 16 wherein the first membrane or the secondmembrane comprises a plurality of different membrane materials toprovide different valve characteristics at specific valve regions. 20.The microfluidic flow control device of claim 16 wherein the pluralityof first control layer channel segments are oriented substantiallyorthogonal to the plurality of second control layer channel segments.21. A microfluidic flow control system comprising the microfluidic flowcontrol device of claim 16 and at least one pressure source.
 22. Themicrofluidic flow control system of claim 21 further comprising acontroller for controlling pressure within individual channel segments.23. The microfluidic flow control system of claim 22, wherein particularfluid flow paths may be selectively programmed via the controller. 24.The microfluidic flow control system of claim 22 further comprising asensor, wherein the controller receives a feedback signal from thesensor.
 25. A microfluidic flow control device comprising: a firstmicrofluidic channel; a second microfluidic channel capable of being influid communication with the first microfluidic channel; at least onedeformable membrane capable of affecting fluid flow between the firstmicrofluidic channel and the second microfluidic channel; at least onemagnetic element associated with the at least one deformable membrane;wherein application of a magnetic field deforms the at least onedeformable membrane.
 26. The microfluidic flow control device of claim25 wherein the at least one magnetic element is bound to or laminatedwithin the at least one deformable membrane.
 27. The microfluidic flowcontrol device of claim 25 wherein the at least one magnetic elementcomprises a discrete magnetic element.
 28. The microfluidic flow controldevice of claim 26 wherein the at least one magnetic element defines afirst aperture, the at least one membrane defines a second aperture, anddeformation of the membrane selectively permits fluid to flow throughthe first aperture and the second aperture.
 29. The microfluidic flowcontrol device of claim 25 further comprising a valve seating surface,wherein the membrane may selectively contact the seating surface.
 30. Amicrofluidic flow control system comprising: the microfluidic flowcontrol device of claim 25; and at least one magnetic field generator.31. The microfluidic flow control system of claim 30 wherein the atleast one magnetic field generator includes a field concentratingelement.
 32. The microfluidic flow control system of claim 30, furthercomprising a controller for controlling the at least one magnetic fieldgenerator.
 33. The microfluidic flow control system of claim 32 whereinthe controller is programmable.
 34. The microfluidic flow control systemof claim 32, further comprising a sensor, wherein the controllerreceives a feedback signal from the sensor.
 35. The microfluidic flowcontrol system of claim 34 wherein the system functions to regulatepressure or fluid flow within at least a portion of the microfluidicdevice.
 36. The microfluidic flow control system of claim 32, whereinthe at least one field generator comprises a plurality of fieldgenerators each having an associated field concentrating element, andwherein the at least one magnetic element comprises a plurality ofdiscrete magnetic elements.
 37. The microfluidic flow control system ofclaim 36, further comprising a plurality of fluidic inlet ports and aplurality of fluidic outlet ports, wherein fluid flow paths between oneor more specific inlet ports and one or more specific outlet ports maybe selectively established.
 38. A configurable microfluidic devicecomprising: a network of interconnected microfluidic channels; aplurality of first control channels; a plurality of second controlchannels; wherein the first control channels and the second controlchannels are separated by one or more deformable membranes from thenetwork of interconnected microfluidic channels at one or moreregulatory regions.
 39. The configurable microfluidic device of claim38, further comprising a control system for controlling the pressure insaid first control channels and in said second control channels.